Energetics Equivalent of the Cardiac Force-Length End-Systolic Zone: Implications for Contractility and Economy of Contraction

Abstract

We have recently demonstrated the existence of a region on the cardiac mechanics stress-length plane, which we have designated "The cardiac end-systolic zone." The zone is defined as the area on the pressure-volume (or stress-length) plane within which all stress-length contraction profiles reach their end-systolic points. It is enclosed by three boundaries: the isometric end-systolic relation, the work-loop (shortening) endsystolic relation, and the zero-active stress isotonic end-systolic relation. The existence of this zone reflects the contraction-mode dependence of the cardiac end-systolic forcelength relations, and has been confirmed in a range of cardiac preparations at the wholeheart, tissue and myocyte levels. This finding has led us to speculate that a comparable zone prevails for cardiac metabolism. Specifically, we hypothesize the existence of an equivalent zone on the energetics plane (heat vs. stress), and that it can be attributed to the recently-revealed heat of shortening in cardiac muscle. To test these hypotheses, we subjected trabeculae to both isometric contractions and work-loop contractions over wide ranges of preloads and afterloads. We found that the heat-stress relations for work-loop contractions were distinct from those of isometric contractions, mirroring the contraction mode-dependence of the stress-length relation. The zone bounded by these contraction-mode dependent heat-stress relations reflects the heat of shortening. Isoproterenol-induced enhancement of contractility led to proportional increases in the zones on both the mechanics and energetics planes, thereby supporting our hypothesis.

Disruption of transverse‐tubular network reduces energy efficiency in cardiac muscle contraction

“…The null effect of detubulation on the peak shortening heat (Figure 4E) is consistent with the non‐significant change of peak shortening extent achieved by trabeculae following detubulation (Figure 6A). The detubulation‐induced reduction in the cardiac end‐systolic zone on the stress‐length plane (Figure 4A) is mirrored by the reduced size of the energetics equivalent “heat‐stress zone” on the heat‐stress plane 63 . The heat‐stress zone is bounded by the work‐loop heat‐stress relation and the isometric heat‐stress relation (Figure 4B), which reflects muscle shortening heat 63 …”

“…The detubulation-induced reduction in the cardiac end-systolic zone on the stress-length plane ( Figure 4A) is mirrored by the reduced size of the energetics equivalent "heat-stress zone" on the heat-stress plane. 63 The heat-stress zone is bounded by the work-loop heat-stress relation and the isometric heat-stress relation ( Figure 4B), which reflects muscle shortening heat. 63 From the discussion above, it is apparent that the effects of detubulation on active heat (Figure 4), are a consequence of reduced peak stress at L o .…”

“…63 The heat-stress zone is bounded by the work-loop heat-stress relation and the isometric heat-stress relation ( Figure 4B), which reflects muscle shortening heat. 63 From the discussion above, it is apparent that the effects of detubulation on active heat (Figure 4), are a consequence of reduced peak stress at L o . The enthalpy output ( Figure 7B) is reduced following detubulation since both work output ( Figure 7A) and heat output (Figure 4) are reduced.…”

Insights From Computational Modeling Into the Contribution of Mechano-Calcium Feedback on the Cardiac End-Systolic Force-Length Relationship

“…The impact of pathological changes on mechano-calcium feedback on cardiac function, in particular, on the ESFLR is not well known. Our recent work demonstrates that in healthy cardiac tissues, the end-systolic zone (defined as the region enclosed by isometric and work-loop ESFLRs; see Han et al, 2019) increases in the presence of isoproterenol-induced enhancement of contractility (Tran et al, 2020). We would expect the end-systolic zone to also be impacted in a disease setting.…”

Cardiac mechanical efficiency is preserved in primary cardiac hypertrophy despite impaired mechanical function

“…Shortening heat is determined by the difference between work-loop and isometric cross-bridge heat, and was slightly (albeit not statistically significantly) decreased in the hypertrophy group. Shortening heat is a well-known concept in the skeletal muscle field, yet was only recently demonstrated to exist in cardiac muscle ( Tran et al, 2017 , 2020 ). The slightly lower shortening heat in trabeculae from hypertrophic rats is consistent with the observed lower extent, and velocity, of shortening.…”